Abstract
Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to post-dihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1203-1211 |
| Number of pages | 9 |
| Journal | Journal of Investigative Dermatology |
| Volume | 106 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 1996 |
| Externally published | Yes |
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Keywords
- alopecia
- C57BL/6
- chemoth erapy
- DOPAchrome
- EPR
- melanin
- tautomerase
- tyrosinase
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology
Cite this
Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a model for studying the melanocyte response to and recovery from cytotoxic drug damage in situ. / Slominski, Andrzej; Paus, Ralf; Plonka, Przemyslaw; Handjiski, Bori; Maurer, Marcus; Chakraborty, Ashok; Mihm, Martin C.
In: Journal of Investigative Dermatology, Vol. 106, No. 6, 01.01.1996, p. 1203-1211.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a model for studying the melanocyte response to and recovery from cytotoxic drug damage in situ
AU - Slominski, Andrzej
AU - Paus, Ralf
AU - Plonka, Przemyslaw
AU - Handjiski, Bori
AU - Maurer, Marcus
AU - Chakraborty, Ashok
AU - Mihm, Martin C.
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to post-dihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.
AB - Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to post-dihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.
KW - alopecia
KW - C57BL/6
KW - chemoth erapy
KW - DOPAchrome
KW - EPR
KW - melanin
KW - tautomerase
KW - tyrosinase
UR - http://www.scopus.com/inward/record.url?scp=0029930653&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029930653&partnerID=8YFLogxK
U2 - 10.1111/1523-1747.ep12348479
DO - 10.1111/1523-1747.ep12348479
M3 - Article
VL - 106
SP - 1203
EP - 1211
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -